基于网络药理学对藏药四味辣根菜汤散抗慢性缺氧性气管炎症的药效物质基础及作用机制研究

低氧在炎症的发展过程中扮演着重要的角色,炎症通过释放炎症因子导致炎症部位的慢性缺氧,并通过转录因子NF-k-B激活HIF-1α的转录,而由于缺氧诱导HIF-1α的表达可激活转录因子NF-k-B及其他炎症因子在炎症部位的表达，加剧炎症的发展。而高原缺氧，更能促使炎症的发展过程，使高原人因肺部疾病而死亡的平均年龄比平原提前。藏药四味辣根菜汤散在高原低氧环境下广泛用于慢性气管炎症的治疗、疗效确切，推测该方从抗炎和调节低氧信号通路两方面发挥协同药效作用。本课题从该方中诸药配伍对化学成分溶出和吸收的影响、入血化学成分、网络药理学，并进一步通过低氧培养人支气管细胞模型（BEAS-2B）和高海拔低氧环境下大鼠慢性气管炎模型来研究其药效，以期阐明四味辣根菜汤散治疗慢性缺氧性气管炎症药效物质基础和作用机理，为高原缺氧性疾病治疗用药和藏药二次开发提供新思路。

Hypoxia play an important role in inflammatory microenvironment. Chronic hypoxia in inflammatory tissue will be casued by inflammation. Another, transcription factor hypoxia-inducible factor (HIF-1α) induced by chronic hypoxia has been demonastrated to further induce and aggravate inflammation by activation of NF-κ-B，Toll-like receptor and other signaling way. And inflammation would be further aggravated by hypoxia in plateau, even more, inhabitant with lung disease living in plateau has shorter lifetime than those living in low altitude. Tibet medicine Siwei-Lagencai-Tang-San has been used to treat and have good effect on chronic bronchitis in the Qinghai-Tibet plateau for centuries. We propose a hypothesis that Tibet medicine Siwei-Lagencai-Tang-San should treat chronic bronchitis by synergism of anti-inflammation and anti-hypoxia. The aim of this study is to clarify that how the compatibility of medicines influence the solubility and absorption of ingredients of Siwei-Lagencai-Tang-San, and to clarify the effect meterial and mechanism based on human bronchial epithelial cell (BEAS-2B) and rat models of chronic bronchitis in hypoxia using serum medicinal chemistry and network pharmacology methods. At last, a reliable and effective method would be established for screening the potentially bioactive components of Tibet medicine Siwei-Lagencai-Tang-San. And all of those will provide a novel approach of "drug-discovery of chronic hypoxic diseases and second development of Tibet medicines.